Abstract

Background

Despite bronchiectasis being increasingly recognised as an important cause of chronic
respiratory morbidity in both indigenous and non-indigenous settings globally, high
quality evidence to inform management is scarce. It is assumed that antibiotics are
efficacious for all bronchiectasis exacerbations, but not all practitioners agree.
Inadequately treated exacerbations may risk lung function deterioration. Our study
tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are
superior to placebo at improving resolution rates of respiratory exacerbations by
day 14 in children with bronchiectasis unrelated to cystic fibrosis.

Methods

We are conducting a

b

ronchiectasis

e

xacerbation

st

udy (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled,
parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland).
In the component of BEST presented here, 189 children fulfilling inclusion criteria
are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg
twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic
acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days.
Clinical data and a paediatric cough-specific quality of life score are obtained at
baseline, at the start and resolution of exacerbations, and at day 14. In most children,
blood and deep nasal swabs are also collected at the same time points. The primary
outcome is the proportion of children whose exacerbations have resolved at day 14.
The main secondary outcome is the paediatric cough-specific quality of life score.
Other outcomes are time to next exacerbation; requirement for hospitalisation; duration
of exacerbation; and spirometry data. Descriptive viral and bacteriological data from
nasal samples and blood markers will also be reported.

Discussion

Effective, evidence-based management of exacerbations in people with bronchiectasis
is clinically important. Yet, there are few randomised controlled trials (RCTs) in
the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs
addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre,
double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic
acid, compared with placebo, improve symptom resolution on day 14 in children with
acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic
response, the role of antibiotic-resistant respiratory pathogens, and whether early
treatment with antibiotics affects duration and time to the next exacerbation, are
also all novel.

Trial registration

Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.